Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori is part of a genus of specialized bacteria that have adapted to the ecological niche provided by gastric mucus. H. pylori has exploited the human niche, while further species of Helicobacter have inhabited the gastric mucosa of other animals. The preferred habitat of H. pylori is the gastric antrum. In humans with normal gastric function, the organism is mainly restricted to the antral surface, where a number of specialized traits allow it to flourish, while causing minimal harm to its host. These include a characteristic motility that allows it to swim rapidly through viscous mucus, and the ability to manufacture large amounts of the enzyme urease. This enzyme breaks down endogenous urea to form ammonia, which protects the bacterium from gastric acidity. Specific adhesions bind a number of the bacteria to the gastric surface, some swim freely in the mucus, and others possibly endocytose into the epithelial cells. It is probably these inaccessible colonization sites that make the organism so difficult to eradicate. In some patients, the normally harmless balance between host and bacterium is disturbed, resulting in peptic ulceration. Modifications to the mucus or epithelial surface in the proximal duodenum, towards the gastric phenotype, make the tissue more susceptible to H. pylori infection of the duodenum by spread of organisms from the antrum. Gastric acid output becomes further increased and the duodenal mucosa is rendered more susceptible to acid attack, leading to peptic ulceration. In other situations, the level of inflammation is enhanced and immunopathology results, followed in the longer term in some cases by atrophy and gastric cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The microbiology and epidemiology of Helicobacter pylori infection. 804 19

Gastric cancer is the world's overall second most common cancer, and carries a bad prognosis. In the Correa model of gastric carcinogenesis, environmental factors (salt, nitrate, a lack of vitamin C and beta-carotene, bile reflux, bacterial overgrowth in atrophic gastritis with nitrosamine formation) are related to the evolution from normal gastric tissue through superficial gastritis, multifocal atrophic gastritis, intestinal metaplasia and dysplasia to carcinoma. The incidence of H. pylori decreases with progressing preneoplastic lesions. In several studies, the prevalence of H. pylori was elevated in patients with gastric cancer, with a trend for a higher prevalence in intestinal type gastric cancer vs diffuse type. Family members of patients with gastric adenocarcinoma have a higher H. pylori prevalence than controls; patients infected with H. pylori have more family members with gastric cancer. Several epidemiological studies showed a higher H. pylori prevalence in regions or populations with high gastric cancer risk vs low-risk populations. Large-scale studies in China and Europe showed a correlation between H. pylori seroprevalence and gastric cancer incidence and mortality. Three prospective nested case-control studies showed that infection with H. pylori increased the risk of further development of gastric adenocarcinoma, showing that H. pylori infection precedes the development of gastric cancer. Several pathways can be identified explaining the association between H. pylori and gastric adenocarcinoma. We showed that gastric cell proliferation is increased in parallel with inflammation. The ascorbic acid concentrating mechanism is abolished in gastritis. Ammonia, generated by H. pylori's urease, gives rise to gastric mucosal atrophy. We showed that salt increases the gastric cell proliferation only in H. pylori-infected individuals. The organism's toxin may play a role in gastric cancer. Besides H. pylori, other environmental factors are important in determining the gastric cancer risk. For instance, we showed that in Belgium, Maghreb immigrants have a high prevalence of H. pylori infection but a low prevalence of intestinal metaplasia and gastric cancer. Gastric lymphoma is rare (about 5% of all gastric tumours), but its incidence is steadily increasing. It was shown that H. pylori also increases the risk for low-grade as well as high-grade gastric lymphoma. Eradication of H. pylori has been shown to cure several cases of unequivocally proven gastric low-grade lymphoma.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Helicobacter pylori: the link with gastric cancer. 806 90

Helicobacter pylori is the cause of chronic active gastritis. It is integral to the pathogenesis of peptic ulcer disease and is epidemiologically linked to gastric cancer and lymphoma. Helicobacter pylori can be detected through a variety of invasive (urease testing, culture, or histologic diagnosis of endoscopic biopsies) and noninvasive (urease breath tests, serologic tests) diagnostic tests. It is now appropriate to detect and eradicate H pylori in patients with a peptic ulcer as the natural history of peptic ulcer disease is then markedly improved. At this time, there is no role for H pylori eradication in the prevention of gastric cancer; however, this concept is being actively investigated. There is no indication to treat patients who have H pylori and nonulcer dyspepsia or gastritis because eradication does not reliably affect their symptoms. Current regimens for eradication include bismuth, antibiotics, and antisecretory agents. Complex and poorly tolerated regimens (triple therapy) may no longer be necessary, as simpler regimens (omeprazole and amoxicillin or clarithromycin) appear to be as effective and better tolerated.
 ...
PMID:Helicobacter pylori. 783 7

This study aimed to determine the importance of raised antibodies to Helicobacter pylori in an asymptomatic population. A total of 128 asymptomatic blood donors who were seropositive for H pylori and consented to endoscopy were investigated. These subjects were from a population of 1010 blood donors screened for antibodies to H pylori. A questionnaire was completed to determine if any subjects had complained of symptoms, and they subsequently had endoscopy. Altogether 121 of 128 were positive for H pylori by histology and urease test and/or culture and all 121 had chronic active gastritis on histology. Twenty five of these subjects had peptic ulcer (20 duodenal, five gastric), a further 21 had erosive duodenitis, and two were found to have gastric cancer. H pylori associated peptic ulcer disease and duodenitis occur more frequently than previously recognised and this suggests that H pylori infection, even if asymptomatic, is of far greater clinical relevance than originally thought.
 ...
PMID:Prevalence of peptic ulcer in Helicobacter pylori positive blood donors. 815 Mar 37

Helicobacter pylori is a Gram-negative bacterium that infects the human gastric mucosa, causes gastritis and contributes to the development of peptic ulcers and gastric cancer. To facilitate molecular genetic analysis of this pathogen, we constructed a approximately 20-fold redundant cosmid library and physical/genetic map of strain NCTC11638. Genomic DNA fragments were cloned into the cosmid vector Lorist6, and clones were ordered by hybridization with several types of probes: (i) ends of cloned DNAs; (ii) chromosomal Notl digest fragments; (iii) cosmids containing Notl sites; and (iv) specific genes. Seven hundred and fifty-one cosmids were mapped to one of three contigs covering > 90% of the chromosome, and are represented by a 68-cosmid miniset. The order of cosmids was confirmed and extents of overlap among them were estimated by restriction analysis. All currently known H. pylori genes were mapped, including those for a cytotoxin (vacA), cytotoxin-associated protein (cagA), urease and regulatory functions (ureAb, ureD and ureH), catalase (katA), major and minor flagellins (flaA and flaB), heat-shock (stress) and chaperone proteins (dnaK, htA, hspB (groEL)), prokaryotic ferritin (pfr), an adhesin subunit (hpaA), a surface protein (26 kDa), and 16S and 23S ribosomal RNAs (two genes each). The orientations of eight genes or clusters were determined, and two repetitive sequences were also found. The gene order and rRNA gene copy number determined here differed from that reported for an unrelated strain, which suggests considerable flexibility in H. pylori genome organization.
 ...
PMID:Ordered cosmid library and high-resolution physical-genetic map of Helicobacter pylori strain NCTC11638. 815 75

The systemic IgG response to Helicobacter pylori was examined in 70 patients with gastric cancer. H pylori IgG antibodies were assayed by enzyme linked immunosorbent assay (ELISA), and serological recognition of H pylori antigens was characterised by western blotting. A percentage of 78.5 were seropositive by ELISA. Two of five patients under age 50 were seronegative. Positivity was unrelated to age, sex, tumour type, or site. Ninety one per cent of ELISA positive cancer patients recognised the H pylori cytotoxin associated 120 kilodalton (kD) protein, significantly more than a control group of 47 ELISA positive patients with non-ulcer dyspepsia (72%). Four of 15 ELISA negative cancer patients also showed recognition of this protein in western blots. Mucosal IgA responses to H pylori were examined by immunoblotting supernatants of in vitro cultured resected antral mucosa in an overlapping group of 19 gastric cancer patients. Eighteen had a positive response, including 10 of 11 negative for H pylori by biopsy urease testing. The systemic and local immunoblotting results show that the high seroprevalence of H pylori antibodies detected by ELISA is nevertheless an underestimate of past infection. Dyspepsia screening policies based solely on H pylori ELISA would miss some young patients with gastric cancer. Further study of the relation of the H pylori cytotoxin to gastric precancerous lesions is warranted.
 ...
PMID:Systemic and mucosal humoral responses to Helicobacter pylori in gastric cancer. 824 98

Research is asking how H. pylori causes diseases, and also why the same bacteria produces different conditions in different persons. The process involves bacterial factors and the host's response. Some bacterial factors such as urease are produced by all strains of H. pylori. This enzyme may damage the gastric epithelium by practically releasing ammonia. Other bacterial factors such as vacuolating toxin are only produced by some strains, and these strains are more likely to cause ulcers or cancer. The host's response has been studied by physiologists, immunologists, and histologists, but the separation of systems is artificial. For example, physiologists find that H. pylori stops gastric D-cells from expressing somatostatin normally, which impairs reflex inhibition of acid secretion, but the D-cell malfunction is probably due to inflammatory factors. In H. pylori gastritis, the gastric epithelial cells behave like immunocytes and express class II molecules and cytokines such as interleukin-8. The patient's histological response to H. pylori is quite closely related to the disease outcome. Patients who respond by developing gastric atrophy are more likely to get gastric ulcers or stomach cancer, but patients whose gastric corpus remains healthy tend to secrete more acid and develop duodenal ulcers, particularly if they have gastric metaplasia in their duodenum. Studies of disease mechanisms provide a valuable insight into the development of these common diseases, and may enable us to identify at-risk groups who particularly merit eradication therapy.
 ...
PMID:Pathogenic mechanisms. 856 49

Helicobacter pylori has been implicated as an agent in the pathogenesis of antral gastritis, gastric and duodenal ulcer and probably in gastric cancer. The C13 urea breath test is a diagnostic method quick to perform, sensitive, reliable and non invasive. It is based on the presence of Helicobacter pylori urease activity, which permits to detect it in the infected mucosa. A substrate (urea) labelled with Carbon 13 is administered to the patient and exhaled breath is collected to detect the possible catabolism product (CO2 labelled with C13). In the European protocol, patients in fasting condition are given a test meal to delay gastric emptying and five minutes later a solution which contents 100 mg of C13 labelled urea. Breath samples are collected before and 30 minutes after urea was given. In our first year of experience, 363 patients with Helicobacter pylori infection detected by histology or urease were studied by C13 urea breath test, with a sensitivity and specificity of 95 and 96%. False negatives may occur if the test is used after antibiotics and other antiulcer drugs. Its main indication is to monitor eradication therapy after treatment. Its possible use as a quantitative test still remains unclear.
 ...
PMID:[C13 urea breath test in the diagnosis of Helicobacter pylori infection in the gastric mucosa. Validation of the method]. 864 14

The International Agency for Research on Cancer, sponsored by the World Health Organization, has recently categorized Helicobacter pylori infection as a class I carcinogen, based on evidence that this infection increases the risk of gastric cancer. The classification was intentionally qualitative in nature and not associated with any public health recommendations. In addition, no specific causal mechanism was proposed to explain the relationship between H. pylori and gastric cancer. In this paper, the magnitude of the risk, implications of the relationship for the prevention of gastric cancer and nature of the causal mechanisms are considered. Relative risk of gastric cancer may be substantial; even with conservative assumptions, the proportion of new cases of gastric cancer worldwide attributable to H. pylori infection is approximately one third of a million annually. This figure is likely to increase with changes in the age structure of the population, and the eradication of H. pylori as a means of prevention of gastric cancer should be considered. A strategy of screening populations in middle age and treating those infected could be relatively inexpensive to administer, but the efficacy is totally unknown and requires evaluation in a randomized controlled trial. Studies designed to address this issue in the general population would need to be large and long-term if gastric cancer is used as an end-point. With respect to carcinogenic mechanisms, a number of constitutive properties of H. pylori may be of relevance to cancer without being specifically carcinogenic. Thus ammonia, which is produced in abundance as a result of urease activity, may promote cell division. Other relevant properties result from the immune response of the host to the bacterium. For example, the excessive production of reactive oxygen metabolites can lead to extensive DNA damage and molecular mutations.
 ...
PMID:Helicobacter pylori and gastric cancer. 872 82

Helicobacter pylori is an important pathogen in humans, causing chronic gastritis and playing a major role in the development of peptic ulcers and gastric cancer. The organism is highly adapted to the human stomach, largely due to its motility and ability to produce large amounts of urease. It binds specifically to the gastric mucosa via adhesion pedestals; colonization of the duodenum only occurs in the presence of gastric metaplasia. Infection with H. pylori leads to gastritis, but the majority of infected patients are asymptomatic, and it is thought that the ability of H. pylori to cause more severe disease may be related to the presence of the cagA gene. With improvements in public health and living conditions, the prevalence of H. pylori infection in developed countries is decreasing, and this is associated with a decline in the incidence of peptic ulcer and gastric cancer.
 ...
PMID:The nature of Helicobacter pylori. 872 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>